This proposal is to establish a Center of Biomedical Research Excellence (COBRE) on the Pathophysiology of neurodegenerative diseases at the University of North Dakota. The overall objective of this Center is to characterize the cellular mechanisms that contribute to neuronal degeneration. The proposed Center will consist of five projects involving 6 junior faculty members, each of which examines a unique aspect of the neurodegenerative process. These five projects, together with the proposed core facilities, faculty recruitments and administrative core will greatly assist us in meeting our long term goal: To develop a highly interactive and collaborative research group focused on understanding the etiology of neurodegeneration and developing therapeutic approaches to prevent or halt neuropathology. The Specific Aims of this COBRE are: 1.) To develop successful independent research projects for the COBRE project directors that will enable them to obtain extramural R01 research grants. 2.) To enhance research infrastructure at the University of North Dakota School of Medicine & Health Sciences (UNDSMHS) through the development of core facilities to support all investigators. 3.) To expand biomedical faculty research in the area of neuroscience through the recruitment of an established senior level neuroscientist and four junior faculty members to UNDSMHS whose research is in the theme of our COBRE. These new faculty recruits will establish a critical mass of researchers at UNDSMHS whose areas of research expertise are in complimentary areas of neuroscience. 4.) To establish a nationally and internationally recognized Center of Neuroscience Research Excellence at the University of North Dakota. The successful completion of COBRE Specific Aims will establish a reputation at UNDSMHS as a Center of Neuroscience Research Excellence that will attract faculty, postdoctoral fellows, and graduate students interested in neuroscience research. Our Center will then be highly competitive for obtaining training grants, program project grants and center grants that will allow for the continuation of the Center of Neuroscience Research Excellence beyond the COBRE award.